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Molecular dynamics study on protein-water interplay in the mechanogating of the bacterial mechanosensitive channel MscL.

Sawada Y, Sokabe M - Eur. Biophys. J. (2015)

Bottom Line: The gating behaviors in this model and the normal MscL model, in which water movements are unrestrained, are compared.This suggests that gate opening relies on a conformational change initiated by wetting.The penetrated water weakens the hydrophobic interaction between neighboring transmembrane inner helices called the "hydrophobic lock" by wedging into the space between their interacting portions.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

ABSTRACT
One of the goals of mechanosensitive channel (MSC) studies is to understand the underlying molecular and biophysical mechanisms of the mechano-gating process from force sensing to gate opening. We focus on the latter process and investigate the role of water in the bacterial MSC MscL, which is activated by membrane tension. We analyze the interplay between water and the gate-constituting amino acids, Leu19-Gly26, through molecular dynamics simulations. To highlight the role of water, specifically hydration of the gate, in MscL gating, we restrain lateral movements of the water molecules along the water-vapor interfaces at the top and bottom of the vapor bubble, plugging the closed gate. The gating behaviors in this model and the normal MscL model, in which water movements are unrestrained, are compared. In the normal model, increased membrane tension breaks the hydrogen bond between Leu19 and Val 23 of the inner helix, exposing the backbone carbonyl oxygen of Leu19 to the water-accessible lumen side of the gate. Associated with this activity, water comes to access the vapor region and stably interacts with the carbonyl oxygen to induce a dewetting to wetting transition that facilitates gate expansion toward channel opening. By contrast, in the water-restrained model, carbonyl oxygen is also exposed, but no further conformational changes occur at the gate. This suggests that gate opening relies on a conformational change initiated by wetting. The penetrated water weakens the hydrophobic interaction between neighboring transmembrane inner helices called the "hydrophobic lock" by wedging into the space between their interacting portions.

No MeSH data available.


Related in: MedlinePlus

a Configuration of amino acids comprising the gate. Residues Leu19, Ala20, Val21, Gly22, Val23, and water molecules are depicted in yellow, red, purple, black, green, and light blue, respectively. b Temporal changes in the interaction energy between the above five amino acids and water induced by increased membrane tension. Black and red lines show the results of the unrestrained and restrained water models, respectively. The interaction energy consists of electrostatic and van der Waals interactions
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Fig6: a Configuration of amino acids comprising the gate. Residues Leu19, Ala20, Val21, Gly22, Val23, and water molecules are depicted in yellow, red, purple, black, green, and light blue, respectively. b Temporal changes in the interaction energy between the above five amino acids and water induced by increased membrane tension. Black and red lines show the results of the unrestrained and restrained water models, respectively. The interaction energy consists of electrostatic and van der Waals interactions

Mentions: As demonstrated in the above results, the backbone carbonyl atoms of Leu19s come to be exposed to the lumen of the pore regardless of the interaction with water. However, the extent of the gate expansion largely differed between the restrained and unrestrained models. To understand how hydration influences subsequent conformational changes of the gate, we calculated the interaction energy between the water molecules and amino acids (Leu19–Val23) constituting the gate in both models. Figure 6 shows the temporal changes in these interaction energies under increased tension. Almost all the interaction energies remained constant during the first 3 ns of the simulation. Thereafter, the Leu19–water and Ala20–water interaction energies gradually decreased in the unrestrained water model (reduced by 30–40 kcal/mol/5 subunits = 6–8 kcal/mol/subunit after 5 ns), whereas both interactions remained almost constant in the restrained water model [Fig. 6(i, ii)]. This result indicates that under increased tension, the value of the interaction energy after 3 ns results from the interaction between carbonyl oxygen of Leu19 and water, and hydration of the gate and the associated conformational changes are energetically favored over a dehydrated gate. Conversely, the closed state of MscL is stabilized by gate dehydration (vapor locking).Fig. 6


Molecular dynamics study on protein-water interplay in the mechanogating of the bacterial mechanosensitive channel MscL.

Sawada Y, Sokabe M - Eur. Biophys. J. (2015)

a Configuration of amino acids comprising the gate. Residues Leu19, Ala20, Val21, Gly22, Val23, and water molecules are depicted in yellow, red, purple, black, green, and light blue, respectively. b Temporal changes in the interaction energy between the above five amino acids and water induced by increased membrane tension. Black and red lines show the results of the unrestrained and restrained water models, respectively. The interaction energy consists of electrostatic and van der Waals interactions
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562998&req=5

Fig6: a Configuration of amino acids comprising the gate. Residues Leu19, Ala20, Val21, Gly22, Val23, and water molecules are depicted in yellow, red, purple, black, green, and light blue, respectively. b Temporal changes in the interaction energy between the above five amino acids and water induced by increased membrane tension. Black and red lines show the results of the unrestrained and restrained water models, respectively. The interaction energy consists of electrostatic and van der Waals interactions
Mentions: As demonstrated in the above results, the backbone carbonyl atoms of Leu19s come to be exposed to the lumen of the pore regardless of the interaction with water. However, the extent of the gate expansion largely differed between the restrained and unrestrained models. To understand how hydration influences subsequent conformational changes of the gate, we calculated the interaction energy between the water molecules and amino acids (Leu19–Val23) constituting the gate in both models. Figure 6 shows the temporal changes in these interaction energies under increased tension. Almost all the interaction energies remained constant during the first 3 ns of the simulation. Thereafter, the Leu19–water and Ala20–water interaction energies gradually decreased in the unrestrained water model (reduced by 30–40 kcal/mol/5 subunits = 6–8 kcal/mol/subunit after 5 ns), whereas both interactions remained almost constant in the restrained water model [Fig. 6(i, ii)]. This result indicates that under increased tension, the value of the interaction energy after 3 ns results from the interaction between carbonyl oxygen of Leu19 and water, and hydration of the gate and the associated conformational changes are energetically favored over a dehydrated gate. Conversely, the closed state of MscL is stabilized by gate dehydration (vapor locking).Fig. 6

Bottom Line: The gating behaviors in this model and the normal MscL model, in which water movements are unrestrained, are compared.This suggests that gate opening relies on a conformational change initiated by wetting.The penetrated water weakens the hydrophobic interaction between neighboring transmembrane inner helices called the "hydrophobic lock" by wedging into the space between their interacting portions.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

ABSTRACT
One of the goals of mechanosensitive channel (MSC) studies is to understand the underlying molecular and biophysical mechanisms of the mechano-gating process from force sensing to gate opening. We focus on the latter process and investigate the role of water in the bacterial MSC MscL, which is activated by membrane tension. We analyze the interplay between water and the gate-constituting amino acids, Leu19-Gly26, through molecular dynamics simulations. To highlight the role of water, specifically hydration of the gate, in MscL gating, we restrain lateral movements of the water molecules along the water-vapor interfaces at the top and bottom of the vapor bubble, plugging the closed gate. The gating behaviors in this model and the normal MscL model, in which water movements are unrestrained, are compared. In the normal model, increased membrane tension breaks the hydrogen bond between Leu19 and Val 23 of the inner helix, exposing the backbone carbonyl oxygen of Leu19 to the water-accessible lumen side of the gate. Associated with this activity, water comes to access the vapor region and stably interacts with the carbonyl oxygen to induce a dewetting to wetting transition that facilitates gate expansion toward channel opening. By contrast, in the water-restrained model, carbonyl oxygen is also exposed, but no further conformational changes occur at the gate. This suggests that gate opening relies on a conformational change initiated by wetting. The penetrated water weakens the hydrophobic interaction between neighboring transmembrane inner helices called the "hydrophobic lock" by wedging into the space between their interacting portions.

No MeSH data available.


Related in: MedlinePlus